scholarly journals Multidrug Resistance Behaviors of Clinical Pseudomonas aeruginosa Strains Associated to Pigment Coloration

2021 ◽  
Author(s):  
Ashish Kothari ◽  
Rohitash Yadav ◽  
Prashant Rajput ◽  
Vanya Singh ◽  
Karanvir Kaushal ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistance ◽  
Antimicrobial Agents ◽  
Vascular System ◽  
Bacterial Pathogen ◽  
Yellow Pigment ◽  
High Morbidity ◽  
Beta Lactam ◽  
Primary Focus ◽  
The Impact

Pseudomonas aeruginosa is an adaptable bacterial pathogen that infects various organs, including the respiratory tract, vascular system, urinary tract, and central nervous system leading to high morbidity and mortality. Our primary focus of this study was to characterize P. aeruginosa clinical strains on the basis of pigment color production, determine its association to multidrug resistance behavior and ability to form biofilm. We identified yellow (30.1%), green (39.8%) and no pigment (30.1%) producing strains from a total of 143 clinical isolates. Yellow pigment producing strains presented significant resistance to a class of antibiotics including β-lactam (91.5%), aminoglycosides (70.5%), and carbapenems (51.9%) compared to green and non-pigmented strains. Importantly, 16.3% of yellow pigment producing strains was resistant to colistin where only 2.3% of non-pigmented and 1.8% of green pigmented strains were resistant to this agent. Moreover, yellow pigment producing strain were frequent producers of β-lactamase group of enzymes, ESBL (55.6%), MBL (55.6%), and AmpC (50%) and displayed higher frequency of efflux positive group (64.2%) compared to green (7.14%) and non-pigmented one (28.5%). Notably, green pigment producing strains when compared to non-pigmented groups also displayed antibiotic susceptibility behavior similar to yellow pigment producing strains. Although yellow pigment producing strains were strong biofilm producers, no significant association was identified between pigment and biofilm formation. Among pigmented and non-pigmented strains, majority of yellow pigment producing strains have shown MIC levels greater than the green and non-pigmented strains. Our study has demonstrated the impact of pigment coloration on susceptibility to antimicrobial agents where yellow pigment producing strains represent considerably a serious problem as due to lack of alternative agents against such transformed strain may collectively be associated with multidrug resistance development.

Putrescine and its metabolic precursor arginine promote biofilm and c-di-GMP synthesis in Pseudomonas aeruginosa

2021 ◽  
Author(s):  
Zhexian Liu ◽  
Sarzana S. Hossain ◽  
Zayda Morales Moreira ◽  
Cara H. Haney
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Immune Responses ◽  
Biofilm Formation ◽  
Antimicrobial Agents ◽  
Bacterial Pathogen ◽  
Guanosine Monophosphate ◽  
Genetic Approach ◽  
Chronic Infections ◽  
Host Immune Responses ◽  
Primary Mechanism

Pseudomonas aeruginosa , an opportunistic bacterial pathogen can synthesize and catabolize a number of small cationic molecules known as polyamines. In several clades of bacteria polyamines regulate biofilm formation, a lifestyle-switching process that confers resistance to environmental stress. The polyamine putrescine and its biosynthetic precursors, L-arginine and agmatine, promote biofilm formation in Pseudomonas spp. However, it remains unclear whether the effect is a direct effect of polyamines or through a metabolic derivative. Here we used a genetic approach to demonstrate that putrescine accumulation, either through disruption of the spermidine biosynthesis pathway or the catabolic putrescine aminotransferase pathway, promoted biofilm formation in P. aeruginosa . Consistent with this observation, exogenous putrescine robustly induced biofilm formation in P. aeruginosa that was dependent on putrescine uptake and biosynthesis pathways. Additionally, we show that L-arginine, the biosynthetic precursor of putrescine, also promoted biofilm formation, but via a mechanism independent of putrescine or agmatine conversion. We found that both putrescine and L-arginine induced a significant increase in the intracellular level of bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) (c-di-GMP), a bacterial second messenger widely found in Proteobacteria that upregulates biofilm formation. Collectively these data show that putrescine and its metabolic precursor arginine promote biofilm and c-di-GMP synthesis in P. aeruginosa . Importance: Biofilm formation allows bacteria to physically attach to a surface, confers tolerance to antimicrobial agents, and promotes resistance to host immune responses. As a result, regulation of biofilm is often crucial for bacterial pathogens to establish chronic infections. A primary mechanism of biofilm promotion in bacteria is the molecule c-di-GMP, which promotes biofilm formation. The level of c-di-GMP is tightly regulated by bacterial enzymes. In this study, we found that putrescine, a small molecule ubiquitously found in eukaryotic cells, robustly enhances P. aeruginosa biofilm and c-di-GMP. We propose that P. aeruginosa may sense putrescine as a host-associated signal that triggers a lifestyle switching that favors chronic infection.

scholarly journals Expression of the multidrug resistance operon mexA-mexB-oprM in Pseudomonas aeruginosa: mexR encodes a regulator of operon expression.

1996 ◽  
Vol 40 (9) ◽  
pp. 2021-2028 ◽  
Author(s):  
K Poole ◽  
K Tetro ◽  
Q Zhao ◽  
S Neshat ◽  
D E Heinrichs ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistance ◽  
Gene Product ◽  
Antimicrobial Agents ◽  
Resistant Mutant ◽  
Multidrug Resistant ◽  
Lacz Fusion ◽  
Base Substitution ◽  
Knockout Mutant

The region upstream of the multiple antibiotic resistance efflux operon mexA-mexB-oprM in Pseudomonas aeruginosa was sequenced, and a gene, mexR, was identified. The predicted MexR product contains 147 amino acids with a molecular mass of 16,964 Da, which is consistent with the observed size of the overexpressed mexR gene product. MexR was homologous to MarR, the repressor of MarA-dependent multidrug resistance in Escherichia coli, and other repressors of the MarR family. A mexR knockout mutant showed a twofold increase in expression of both plasmid-borne and chromosomal mexA-reporter gene fusions compared with the MexR+ parent strain, indicating that the mexR gene product negatively regulates expression of the mexA-mexB-oprM operon. Furthermore, the cloned mexR gene product reduced expression of a plasmid-borne mexA-lacZ fusion in E. coli, indicating that MexR represses mexA-mexB-oprM expression directly. Consistent with the increased expression of the efflux operon in the mexR mutant, the mutant showed an increase (relative to its MexR+ parent) in resistance to several antimicrobial agents. Expression of a mexR-lacZ fusion increased threefold in a mexR knockout mutant, indicating that mexR is negatively autoregulated. OCR1, a nalB multidrug-resistant mutant which overproduces OprM, exhibited a greater than sevenfold increase in expression of a chromosomal mexA-phoA fusion compared with its parent. Introduction of a mexR knockout mutation in strain OCR1 eliminated this increase in efflux gene expression and, as expected, increased the susceptibility of the strain to a variety of antibiotics. The nucleotide sequences of the mexR genes of OCR1 and its parental strain revealed a single base substitution in the former which would cause a predicted substitution of Trp for Arg at position 69 of its mexR product. These data suggest that MexR possesses both repressor and activator function in vivo, the activator form being favored in nalB multidrug-resistant strains.

scholarly journals The Role of Streptococcus pneumoniae in Community-Acquired Pneumonia

2020 ◽  
Vol 41 (04) ◽  
pp. 455-469 ◽  
Author(s):  
Charles Feldman ◽  
Ronald Anderson
Keyword(s):  
Antibiotic Resistance ◽  
Streptococcus Pneumoniae ◽  
Antimicrobial Agents ◽  
Bacterial Pathogen ◽  
Epidemiological Data ◽  
The United States ◽  
Invasive Infection ◽  
Geographic Variations ◽  
The Impact

AbstractWith the notable exceptions of the United States and Canada in particular, the global burden of disease in adults due to invasive infection with the dangerous respiratory, bacterial pathogen, Streptococcus pneumoniae (pneumococcus) remains. This situation prevails despite the major successes of inclusion of polysaccharide conjugate vaccines (PCVs) in many national childhood immunization programs and associated herd protection in adults, as well as the availability of effective antimicrobial agents. Accurate assessment of the geographic variations in the prevalence of invasive pneumococcal disease (IPD) has, however, been somewhat impeded by the limitations imposed on the acquisition of reliable epidemiological data due to reliance on often insensitive, laboratory-based, pathogen identification procedures. This, in turn, may result in underestimation of the true burden of IPD and represents a primary focus of this review. Other priority topics include the role of PCVs in the changing epidemiology of IPD in adults worldwide, smoking as a risk factor not only in respect of increasing susceptibility for development of IPD, but also in promoting pneumococcal antibiotic resistance. The theme of pneumococcal antibiotic resistance has been expanded to include mechanisms of resistance to commonly used classes of antibiotics, specifically β-lactams, macrolides and fluoroquinolones, and, perhaps somewhat contentiously, the impact of resistance on treatment outcome. Finally, but no less importantly, the role of persistent antigenemia as a driver of a chronic, subclinical, systemic proinflammatory/procoagulant phenotype that may underpin the long-term sequelae and premature mortality of those adults who have recovered from an episode of IPD, is considered.

Effect of a Program to Reduce Hospital Ciprofloxacin Use on Nosocomial Pseudomonas aeruginosa Susceptibility to Quinolones and Other Antimicrobial Agents

2008 ◽  
Vol 29 (8) ◽  
pp. 716-722 ◽  
Author(s):  
Paul P. Cook ◽  
Titu D. Das ◽  
Michael Gooch ◽  
Paul G. Catrou
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Agents ◽  
Tertiary Care ◽  
Regression Analyses ◽  
Antimicrobial Management ◽  
Management Effort ◽  
The Mean ◽  
Ciprofloxacin Resistance ◽  
The Impact ◽  
Susceptibility Patterns

Objective.We evaluated the effect of an antimicrobial management effort to decrease ciprofloxacin use on the antibiotic susceptibility of nosocomial Pseudomonas aeruginosa isolates.Design.Retrospective, observational study.Setting.Tertiary care teaching hospital with 731 beds.Methods.The study was conducted between January 1, 2001, and December 31, 2007. Linear regression analyses and Student t tests were used to determine significant changes in drug use among patients and antimicrobial susceptibility patterns among nosocomial P. aeruginosa isolates during the 84-month period.Results.Following implementation of a program to reduce oral and intravenous use of ciprofloxacin in 2005, there was a 56.6% reduction in ciprofloxacin use (P < .001). Significant reductions in the mean percentage of nosocomial P. aeruginosa isolates that were resistant to ciprofloxacin (from 45.0% to 35.2%; P < .002) and the mean incidence of ciprofloxacin resistance (from 0.77 to 0.67 isolates recovered per 1,000 patient-days; P = .03) were noted after implementation of this program. The total quantity of antipseudomonal antibiotics consumed decreased, but the use of certain antipseudomonal antibiotics (ie, cefepime and imipenem/meropenem) increased. Among nosocomial P. aeruginosa isolates, the prevalence of imipenem/meropenem resistance increased, whereas the prevalence of cefepime resistance did not. During the 84 months of the study, there was a significant association between ciprofloxacin use and the percentage of nosocomial P. aeruginosa isolates that were resistant to ciprofloxacin (p = 0.47; P = .011), but there was no correlation between ciprofloxacin use and the incidence of ciprofloxacin resistance (p = 0.21; P = .26).Conclusions.Major reductions in ciprofloxacin use were associated with small but significant improvements in the rate of ciprofloxacin susceptibility among nosocomial P. aeruginosa isolates. The impact of the program on other antipseudomonal agents was variable.

scholarly journals Impact of Multidrug-Resistant Pseudomonas aeruginosa Bacteremia on Patient Outcomes

2010 ◽  
Vol 54 (9) ◽  
pp. 3717-3722 ◽  
Author(s):  
Vincent H. Tam ◽  
Cary A. Rogers ◽  
Kai-Tai Chang ◽  
Jaye S. Weston ◽  
Juan-Pablo Caeiro ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistance ◽  
Patient Outcomes ◽  
Significant Risk ◽  
Empirical Therapy ◽  
Multidrug Resistant ◽  
Classification And Regression Tree ◽  
Apache Ii Score ◽  
Continuous Variables ◽  
The Impact

ABSTRACT Trends of rising rates of resistance in Pseudomonas aeruginosa make selection of appropriate empirical therapy increasingly difficult, but whether multidrug-resistant (MDR) P. aeruginosa is associated with worse clinical outcomes is not well established. The objective of this study was to determine the impact of MDR (resistance to three or more classes of antipseudomonal agents) P. aeruginosa bacteremia on patient outcomes. We performed a retrospective cohort study of adult patients with P. aeruginosa bacteremia from 2005 to 2008. Patients were identified by the microbiology laboratory database, and pertinent clinical data were collected. Logistic regression was used to explore independent risk factors for 30-day mortality. Classification and regression tree analysis was used to determine threshold breakpoints for continuous variables. Kaplan-Meier survival analysis was used to compare time to mortality, after normalization of the patients' underlying risks by propensity scoring. A total of 109 bacteremia episodes were identified; 25 episodes (22.9%) were caused by MDR P. aeruginosa. Patients with MDR P. aeruginosa bacteremia were more likely to receive inappropriate empirical therapy (44.0% and 6.0%, respectively; P < 0.001) and had longer prior hospital stays (32.6 ± 37.3 and 14.4 ± 43.6 days, respectively; P = 0.046). Multivariate regression revealed that 30-day mortality was associated with multidrug resistance (odds ratio [OR], 6.8; 95% confidence interval [CI], 1.9 to 24.0), immunosuppression (OR, 5.0; 95% CI, 1.4 to 17.5), and an APACHE II score of ≥22 (OR, 29.0; 95% CI, 5.0 to 168.2). Time to mortality was also shorter in the MDR cohort (P = 0.011). Multidrug resistance is a significant risk factor for 30-day mortality in patients with P. aeruginosa bacteremia; efforts to curb the spread of MDR P. aeruginosa could be beneficial.

scholarly journals A Study of Isolation and Identification of Multidrug Resistant Pseudomonas aeruginosa from Wound Specimen

2020 ◽  
pp. 26-31
Author(s):  
Maria Muddassir ◽  
Sadaf Munir ◽  
Almas Raza ◽  
Adeel Iqbal ◽  
Muddassir Ahmed ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistance ◽  
Antimicrobial Agents ◽  
Morphological Characteristics ◽  
Multidrug Resistant ◽  
Hospitalized Patients ◽  
Clinical Samples ◽  
Isolation And Identification ◽  
Antimicrobial Drugs ◽  
Antibiotic Resistant

Background: Pseudomonas aeruginosa is a clinically important pathogenic microbe in hospitalized patients. It is a major cause of mortality and morbidity having a number of mechanisms that make it antibiotic resistant. Considering the dearth of antimicrobial drugs to treat infection with this pathogen, it has become a necessity to open up new arena for treatment with this organism. Recently, there has been an up rise in the number of multidrug resistant pathogenic strains of Pseudomonas aeruginosa. Objective: Isolation and identification of multidrug resistant Pseudomonas aeruginosa from wound specimens and to evaluate the antibiotic resistant strains of this microbe. Methodology: One hundred and fifty clinical samples of wound were taken from hospitalized patients at Jinnah hospital Lahore during the period of October 2019 to April 2020. In total, twenty (20) isolates of Pseudomonas aeruginosa were identified using the cultural features, morphological characteristics and various biochemical tests plus the Vitek 2 system. Blue/green, brown /blue and yellow/green pigment production showed the presence and growth of Pseudomonas aeruginosa. Results: Percentage of Pseudomonas aeruginosa in females came out to be 15% as compared to 11.42% in males. This was followed by testing susceptibility of isolates of Pseudomonas aeruginosa to various antimicrobial drugs. Piperacillin/tazobactam and meropenem showed the highest efficacy against Pseudomonas aeruginosa. Highest resistance was exhibited against trimethoprim/sulfamethoxazole which was 75%. Conclusion: Most isolates showed multidrug resistance to four or more drugs. Development of multidrug resistance has emerged as a global problem with pathogens commonly causing infections becoming increasingly resistant to antimicrobial agents.

scholarly journals 150. Improved Susceptibility of Pseudomonas aeruginosa to Cefepime (CEF) at a Veterans Tertiary Care Hospital, over a 7-Year Period (2011-2017): The Impact of Antibiotic Rotation/Cycling and Reversal of Drug Resistance in P. aeruginosa

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S187-S187
Author(s):  
Ryan Kuhn ◽  
Oscar Martinez ◽  
Chris Ross ◽  
Lauren Touleyrou ◽  
Suganthini Krishnan Natesan
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Drug Resistance ◽  
Pearson Correlation ◽  
Tertiary Care ◽  
Laboratory Data ◽  
High Morbidity ◽  
Care Hospital ◽  
Drug Shortage ◽  
Antibiotic Cycling ◽  
The Impact

Abstract Background Background: Pseudomonas aeruginosa continues to be an important cause of nosocomial infections associated with a high morbidity and mortality. Despite the availability of ceftazidime-avibactam (CAZ-AVI) and ceftolozone-tazobactam (CFT-TAZO), CEF continues to be an empiric agent of choice in several institutions. Aim: To evaluate the prevalence and trend in susceptibilities of P. aeruginosa to CEF over a 7-year period, identify possible correlation with the use of CAZ, AZT, PTZ, CIP, and CAR, (DOT/1000 patient days), as a quality improvement (QI) measure for optimizing CEF use, introduce antibiotic cycling as a tool to avoid emergence of drug-resistance in P. aeuriginosa. Methods A retrospective review of antimicrobial susceptibility data of all isolates of P. aeruginosa, (inpatient and outpatient) at the Detroit VAMC pre and post implementation of antibiotic cycling, over a 7-year period (2011-2017) was performed. Susceptibility testing was performed by reference broth micro-dilution methods in a central laboratory. Data analysis was performed using Pearson correlation coefficient score. Being a QI project, clinical data were not reviewed. Results A total of 977 isolates were identified during the study period. (drug usage are in DOT/1000 PD); CAZ and AZT use surged during 2013-14 from 5 to 8 dropping in 2015-17 to &lt; 3; PTZ usage increased to 100 during 2011-14 but dropped to 38 in 2015-17 (drug shortage); CAR use averaged at 10 until 2016 and dropped to 8 in 2017; CIP use dropped by 50% from 30 in 2012 to 15 in 2017; P. aeruginosa susceptible to CEF decreased from 88% in 2012 to 81% in 2014 mirroring the increased use of CEF, AZT, CAZ, and CIP; AG use was very low at &lt; 5. With restrictions on the use of AZT, CAZ, and CIP, from 2014-15, CEF susceptibility increased significantly to 95.5% in 2015. Drug shortage of PTZ in 2015 and increased use of CEF from 2015-17 led to a drop in susceptibility to (82%); P. aeruginosa susceptible to CAR and AG averaged at 88% and 97% respectively (2011-17). However, reintroduction PTZ, resulted in improved susceptibility of P. aeuruginosa to CEF by 40% within a year. Conclusion Judicious antimicrobial use and antibiotic rotation play a significant role in reversing drug resistance in P. aeuruginosa. Disclosures All Authors: No reported disclosures

scholarly journals Bacterial Nosocomial Infections: Multidrug Resistance as a Trigger for the Development of Novel Antimicrobials

Antibiotics ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 942
Author(s):  
Sílvia A. Sousa ◽  
Joana R. Feliciano ◽  
Tiago Pita ◽  
Catarina F. Soeiro ◽  
Beatriz L. Mendes ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Nosocomial Infections ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Healthcare Systems ◽  
High Morbidity ◽  
Therapeutic Approaches ◽  
New Compounds ◽  
Novel Therapeutic

Nosocomial bacterial infections are associated with high morbidity and mortality, posing a huge burden to healthcare systems worldwide. The ongoing COVID-19 pandemic, with the raised hospitalization of patients and the increased use of antimicrobial agents, boosted the emergence of difficult-to-treat multidrug-resistant (MDR) bacteria in hospital settings. Therefore, current available antibiotic treatments often have limited or no efficacy against nosocomial bacterial infections, and novel therapeutic approaches need to be considered. In this review, we analyze current antibacterial alternatives under investigation, focusing on metal-based complexes, antimicrobial peptides, and antisense antimicrobial therapeutics. The association of new compounds with older, commercially available antibiotics and the repurposing of existing drugs are also revised in this work.

scholarly journals COMMUNITY-ACQUIRED PNEUMONIA IN INFECTIOUS HOSPITAL PATIENTS: THE DEVELOPMENT OF RESISTANCE TO ANTIMICROBIALS

2018 ◽  
Vol 23 (3) ◽  
pp. 108-113
Author(s):  
Marina G. Avdeeva ◽  
G. V. Shubina ◽  
A. A. Ganzha ◽  
E. V. Zhuravleva
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Agents ◽  
Resistance Mechanisms ◽  
Community Acquired Pneumonia ◽  
Diffusion Method ◽  
Individual Risk ◽  
Beta Lactam ◽  
Local Data ◽  
Antimicrobial Drugs

The aim of the work was to study the structure, level and dynamics of resistance to antimicrobial drugs of the most common types of microorganisms in patients with community-acquired pneumonia (CAP) in the Krasnodar Territory, on the example of patients treated in a regional specialized infectious hospital for the period 2015-2017. Materials and methods. The results of bacteriological tests of expectoration, including 523 positive strains of microorganisms, are analyzed. The analysis does not include strains with hospital multidrug resistance. A bacterioscopy with Gram stain and sputum seeding on plate-like artificial nutrient media were carried out. Identification of the pathogen was performed by mass spectrometry using MALDI-TOF technology (Microflex LT, Bruker, Germany), phenotypically identified resistance mechanisms were confirmed on the automatic analyzer Vitek II Compact (BioMérieux, France). The sensitivity to antimicrobials was determined by the disc-diffusion method in the Müller-Hinton medium, using the disks by Bio-Rad, France. The antibioticogram was analyzed on the apparatus “Adagio” (Bio-Rad, France). Results. In the etiologic structure of community-acquired pneumonia, Streptoccocus pneumonia prevails in patients hospitalized in an infectious hospital in the Krasnodar Territory, which is determined in 73.56% of confirmed cases, which is twice as high as an average in Russia. Staphylococcus aureus was determined in 9.04% of casesd, with fluctuations in different years from 3.8% to 12.1%. Klebsiella pneumoniae was found in 4.61%, with variations from 1.7% to 9.3%. Pseudomonas aeruginosa was registered in 4.6%, altered from 1.3% to 7.8%. Other microorganisms were represented with Enterobacteriaceae family, 8.2% of the cases. The resistance of wild strains of microorganisms isolated at CAP to a number of antimicrobial agents has been established. A number of negative trends were noted: the emergence of pneumococcal strains resistant to beta-lactam antimicrobial drugs (benzylpenicillin MIC < 2μg); an increase in the resistance of pneumococci to macrolides, tetracyclines, sulfonamides. There is a high percentage of Staphylococcus aureus (80%) producing penicillinase, and an increase in their resistance to macrolides. A high level of Pseudomonas aeruginosa resistance to 3-rd and 4-th generation cephalosporins is noted. Conclusion. The obtained data determine the need for further monitoring of regional resistance of microorganisms, which will allow both adequate start therapy and the possibility of its timely correction. In the practical work of a doctor, it is important not only to be guided by local data on the resistance of microorganisms to antimicrobial drugs, but also to analyze the possible causes of its occurrence with the establishment of individual risk factors.

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